Gut microbiota mediate melatonin signalling in association with type 2 diabetes.

AIMS/HYPOTHESIS: It has been shown that melatonin plays a general beneficial role in type 2 diabetes in rodents but its role in humans is controversial. In the present study, we investigated the association between serum melatonin and type 2 diabetes risk in a southern Chinese population in a case-control study. We also examined the role of gut microbiota in this relationship. METHODS: Individuals with type 2 diabetes (cases) and healthy individuals (controls) (n=2034) were recruited from a cross-sectional study and were matched for age and sex in a case-control study. The levels of serum melatonin were measured and the association between serum melatonin and type 2 diabetes risk was examined using a multivariable logistic regression model. We further conducted a rigorously matched case-control study (n=120) in which gut microbial 16S rRNA was sequenced and metabolites were profiled using an untargeted LC-MS/MS approach. RESULTS: Higher levels of serum melatonin were significantly associated with a lower risk of type 2 diabetes (OR 0.82 [95% CI 0.74, 0.92]) and with lower levels of fasting glucose after adjustment for covariates (ß -0.25 [95% CI -0.38, -0.12]). Gut microbiota exhibited alteration in the individuals with type 2 diabetes, in whom lower levels of serum melatonin, lower α- and ß-diversity of gut microbiota (p<0.05), greater abundance of Bifidobacterium and lower abundance of Coprococcus (linear discriminant analysis [LDA] >2.0) were found. Seven genera were correlated with melatonin and type 2 diabetes-related traits; among them Bifidobacterium was positively correlated with serum lipopolysaccharide (LPS) and IL-10, whereas Coprococcus was negatively correlated with serum IL-1ß, IL-6, IL-10, IL-17, TNF-α and LPS (Benjamini-Hochberg-adjusted p value [false discovery rate (FDR)] <0.05). Moreover, altered metabolites were detected in the participants with type 2 diabetes and there was a significant correlation between tryptophan (Trp) metabolites and the melatonin-correlated genera including Bifidobacterium and Coprococcus (FDR<0.05). Similarly, a significant correlation was found between Trp metabolites and inflammation factors, such as IL-1ß, IL-6, IL-10, IL-17, TNF-α and LPS (FDR<0.05). Further, we showed that Trp metabolites may serve as a biomarker to predict type 2 diabetes status (AUC=0.804). CONCLUSIONS/INTERPRETATION: A higher level of serum melatonin was associated with a lower risk of type 2 diabetes. Gut microbiota-mediated melatonin signalling was involved in this association; especially, Bifidobacterium- and Coprococcus-mediated Trp metabolites may be involved in the process. These findings uncover the importance of melatonin and melatonin-related bacteria and metabolites as potential therapeutic targets for type 2 diabetes.

Dietary variety relates to gut microbiota diversity and abundance in humans.

PURPOSE: We aim to investigate the relationship between gut microbiota and dietary variety in a Chinese population using Dietary Variety Score (DVS), an index of dietary variety, as little has studied the relationship of dietary variety and gut microbiota in a general population. METHODS: In this cross-sectional study, recruited participants were conducted with face-to-face interview to collect information on 24-h food intake and dietary consumption using a valid food frequency questionnaire. Subjects (n = 128) were divided as high and low DVS groups by the median of DVS after rigorously matching for confounding factors. The gut microbiota was assessed by 16S rRNA sequencing and the correlations between key phylotypes and DVS, Index of Nutritional Quality (INQ) and clinical indices were examined using generalized linear model in negative binomial regression. RESULTS: Higher score of DVS, INQVB6, INQVE and INQZn exhibited higher α-diversity. DVS was correlated with INQ and six genera. Among the DVS-correlated genera, Turicibacter, Alistipes and Barnesiella were positively correlated with INQVE, INQZn and INQCu, individually or in combination, while Cetobacterium was negatively correlated with INQCu, INQZn and INQVE. The abundance of Coprococcus and Barnesiella increased with the elevated cumulative scores of INQVE, INQVB6 and INQZn. The combination of Alistipes, Roseburia and Barnesiella could moderately predict dietary variety status. CONCLUSION: Higher DVS was correlated with higher microbial diversity and more abundance of some potentially beneficial bacteria but with less some potentially pathogenic bacteria. A high variety dietary, therefore, should be recommended in our daily life.

Role of PCK1 gene on oil tea-induced glucose homeostasis and type 2 diabetes: an animal experiment and a case-control study.

BACKGROUND: Oil tea is a type of traditional tea beverage used for treating various ailments in minority population in Guangxi, China. Our previous study showed oil tea improved glucose and lipid levels in type 2 diabetic mice. Yet, the underling molecular mechanisms are still not understood. This study aimed at assessing the effect of oil tea on glucose homeostasis and elucidating the molecular mechanisms underlying the oil tea-induced antidiabetic effects. METHODS: Twenty seven db/db mice were gavaged with saline, metformin and oil tea for 8 weeks with measurement of biochemical profiles. A real-time2 (RT2) profiler polymerase chain reaction (PCR) array comprising 84 genes involved in glucose metabolism was measured and validated by quantitative PCR (qPCR). The association between the candidate genes and type 2 diabetes were further analyzed in a case-control study in the Chinese minority population. RESULTS: Oil tea treatment facilitated glucose homeostasis by decreasing fasting blood glucose and total cholesterol, and improving glucose tolerance. Suppressing phosphoenolpyruvate carboxykinase 1 (PCK1) expression was observed in the oil tea treatment group and the expression was significantly correlated with fasting blood glucose levels. Target prediction and functional annotation by WEB-based GEne SeT AnaLysis Toolkit (WebGestalt) revealed that PCK1 mainly involved in the glycolysis/gluconeogenesis pathway among the top Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathways. Both rs707555 and rs2071023 in PCK1 were significantly associated with type 2 diabetes in the minority population of Guangxi. CONCLUSION: Our findings indicated oil tea improved glucose homeostasis via down-regulation of PCK1 and PCK1 may be a genetic marker for the treatment of type 2 diabetes.